Method for separating and purifying heparin sodium and heparan sulfate from heparin byproducts

Abstract

The invention discloses a method for separating and purifying heparin sodium and heparan sulfate from heparin byproducts. The method comprises the steps of dissolving raw heparin byproducts, adding potassium acetate to precipitate and separate heparin sodium, adding potassium acetate to precipitate heparin sodium after precipitating and dissolving heparin sodium, collecting a precipitate, dissolving and then conducting fractional precipitation repeatedly with anhydrous alcohol to prepare the heparin sodium with a higher purity, adding a benedict reagent and a saturated sodium hydroxide solution to supernate, centrifuging to obtain a solution containing the heparan sulfate, removing copper ions with a decoppering agent, adding active carbon to absorb the precipitate, decolorizing and filtering, and then absorbing and eluting with anion exchange resin to obtain the high-purity heparan sulfate by separation. According to the method, the high-purity heparin sodium and heparan sulfate can be separated again from the byproducts used for producing the heparin sodium, so that financial resources and material resources required for storing or discarding a large number of heparin byproducts can be saved, wastes can be changed into valuables, the byproducts are recycled, the cost is saved greatly, and a value is created.

Description

technical field [0001] The invention relates to a method for separating and purifying heparin sodium and heparan sulfate from heparin by-products, belonging to the field of mucopolysaccharide biopharmaceuticals. Background technique [0002] Heparin sodium is a mucopolysaccharide sulfate anticoagulant drug. In recent years, studies have proved that heparin sodium also has the effect of lowering blood lipids. Heparan sulfate is a subfraction of heparin, present in unfractionated heparin. Compared with heparin sodium, heparan sulfate has the advantage of moderate anticoagulant activity. Heparan sulfate is used for antithrombotic, anti-inflammatory, hypolipidemic, and renal protection of diabetic patients, and is the most researched mucopolysaccharide biochemical drug in recent years. [0003] A large number of by-products, i.e. heparin by-products, are produced in the process of producing heparin from the porcine small intestinal mucosa through ion exchange and fractional pr...

AI Technical Summary

Problems solved by technology

However, due to the difficulty in separating the effective substances, these by-products are generally discarded or stored after heparin production, or simply processed, such as the traditional process is mainly to purify heparan sulfate and dermatan sulfate from heparin by-products, and heparin sodium discarded, resulting in a certain loss

Heparan sulfate and dermatan sulfate have similar properties, and it is difficult to purify heparan sulfate by conventional ion exchange chromatography and fractional precipitation with organic solvents

In the prior art, the special reaction between heparan sulfate and dermatan sulfate and Benedict's reagent is used to separate the two, but the separated heparan sulfate solution contains a large amount of copper ions

The patent (200910039359.9) removes copper ions by adsorption and washing of ion-exchange chromatography columns, which not only easily reduces the life of the resin, but also makes it difficult to remove copper ions, so that the crude heparan sulfate still has a light blue color. Determination, the copper ion content exceeds 30ppm